Involvement of mouse cerebellar neuronal nitric oxide synthase (nNOS)‎ system in the functional interaction and cross-tolerance between nicotine and ethanol

الملخص EN

Individuals who smoke tobacco overwhelmingly drink alcohol and vice versa.

We previously observed functional interaction and cross-tolerance between alcohol and intracerebellar (ICB) nicotine.

We now report their mediation by cerebellar nNOS in male CD-1 mice.

Nicotine and nNOS inhibitor (nNOSI); N-[(4S)-4-amino-5- [(2-aminoethyl)amino]pentyl]-N-nitroguanidine tris(trifluoroacetate) salt, were directly infused into the cerebellum while ethanol was injected IP.

Ethanol (2 g/kg)-induced ataxia (EIA) was potentiated by nNOSI (0.1, 0.5, 1.0 ng) suggesting nNOS-mediation.

Pretreatment with nNOSI (0.5, 1.0, 2.0 ng) dose-dependently antagonized nicotine (5 ng)-induced attenuation of EIA suggesting involvement of cerebellar nNOS.

When nNOSI (0.5, 1.0, 2.0 ng) and nicotine (5 ng) were microinfused once daily for 5 days, followed 16 h later by ethanol, virtual absence of cross-tolerance was noted.

However, when aCSF was infused instead of nNOSI, robust cross-tolerance was noted confirming mediation by cerebellar nNOS system.

Overall, these results support role of the cerebellar nNOS in cross-tolerance between ethanol and nicotine.